Management of the aortic arch in patients with Loeys-Dietz syndrome.

OBJECTIVES: We sought to develop strategies for management of the aortic arch in patients with Loeys-Dietz syndrome (LDS) through a review of our clinical experience with these patients and a comparison with our experience in patients with Marfan syndrome (MFS). METHODS: We reviewed hospital and follow-up records of 79 patients with LDS and compared them with 256 patients with MFS who served as reference controls. RESULTS: In the LDS group, 16% of patients presented initially with acute aortic dissection (AAD) (67% type A, 33% type B) or developed AAD during follow-up, compared with 10% of patients with MFS (95% type A, 5% type B). There was no difference between patients with LDS or MFS in need for subsequent arch interventions after aortic root surgery (46% vs 50%, P = 1.0). Among the patients who never had AAD, the need for arch repair at initial root surgery was greater in patients with LDS (5% vs 0.4%, P = .04), as was the need for any subsequent aortic surgery (12% vs 1.3%, P = .0004). Late mortality in patients with LDS after arch repair was greater than in those patients who had no arch intervention (33% vs 6%, P = .007). CONCLUSIONS: In the absence of dissection, patients with LDS have a greater rate of arch intervention after root surgery than patients with MFS. After a dissection, arch reintervention rates are similar in the 2 groups. Arch intervention portends greater late mortality in LDS.

Prognostic and Predictive Clinicopathologic Factors of Squamous Anal Canal Cancer in HIV-Positive and HIV-Negative Patients: Does HAART Influence Outcomes?

BACKGROUND: The incidence of squamous cell carcinoma (SCC) of the anal canal has been rising over the past decades, especially in patients infected with human immunodeficiency virus (HIV). Despite the advent of potent multidrug regimens to treat HIV-termed highly active antiretroviral therapy (HAART), anal SCC rates have not declined, and the impact of HAART on anal SCC remains controversial. AIM: The purpose of this study was to define outcomes of anal SCC treatment in HIV-positive and HIV-negative patients. METHODS AND MATERIALS: A retrospective single-institution analysis was performed on all patients with anal SCC treated at the Johns Hopkins Hospital between 1991 and 2010. The primary outcomes measured were 5-year overall survival (5-year OS), median survival, and relapse rates. RESULTS: Our search identified 93 patients with anal SCC. Patients had a mean age of 54 years; 37.6% were male, and 21.5% were HIV-positive. Median follow-up was 28 months. Relapse occurred in 16.1% of patients. Median time to relapse was 20 months. Relapse rates were slightly higher with HIV-positive versus negative patients (30.0 vs. 12.3%) but did not reach statistical significance (p = 0.06). Among HIV-positive patients, those who relapsed were more likely to be on HAART than those who did not relapse (83.3 vs. 14.3%, p = 0.007). 5-year OS was 58.9% for the total group of patients with no significant difference between those who relapsed versus those who did not (76.2 vs. 54.5%, p = 0.20). No survival difference was seen between HIV-positive and negative patients. Survival was associated with AJCC stage in all patients. CONCLUSION: In our small series, HIV infection was not associated with a significantly higher relapse rate or worse 5-year OS among patients with anal SCC. HAART was associated with a higher rate of relapse in HIV-positive patients. AJCC staging predicted survival in both relapsed and non-relapsed patients regardless of HIV status.

Validation of a Real-Time Minute-to-Minute Urine Output Monitor and the Feasibility of Its Clinical Use for Patients Undergoing Cardiac Surgery.

Acute kidney injury after cardiac surgery is associated with increased morbidity and mortality. Methods for measuring urine output in real time may better ensure renal perfusion perioperatively in contrast to the current standard of care where urine output is visually estimated after empiric epochs of time. In this study, we describe an accurate method for monitoring urine output continuously during cardiopulmonary bypass. This may provide a means for setting patient-specific targets for blood pressure and cardiopulmonary bypass flow as a potential strategy to reduce the risk for acute kidney injury.

Preoperative Staphylococcus Aureus Screening and Targeted Decolonization in Cardiac Surgery.

BACKGROUND: We assessed the impact of preoperative Staphylococcus aureus screening and targeted decolonization on the incidence of postoperative methicillin-resistant S aureus (MRSA) colonization, intensive care unit MRSA transmission, and surgical site infections in cardiac surgery patients. METHODS: We reviewed medical records for all adult patients during two periods: preintervention (January 2007 to April 2010) and intervention (January 2011 to December 2014). In the intervention period, we performed nasal screening for methicillin-sensitive S aureus and MRSA using polymerase chain reaction within 30 days of the operation. Colonized patients received intranasal mupirocin twice daily and chlorhexidine baths daily for 5 days; patients colonized with MRSA also received prophylactic vancomycin plus cefazolin with contact isolation precautions. Nasal surveillance for MRSA was performed on intensive care unit admission and weekly thereafter. Multivariable logistic regression models were constructed to determine risk factors for postoperative MRSA colonization, and surgical site infections and the impact of our screening program was assessed in these models. Poisson regression was used to assess MRSA transmission. RESULTS: Comparing 2,826 preintervention and 4,038 intervention patients, cases differed in age, diabetes mellitus, preoperative infection, preoperative length of stay, and bypass time (all p ≤ 0.03). Intervention patients had risk-adjusted reductions in MRSA colonization (odds ratio 0.53, 95% confidence interval [CI]: 0.37 to 0.76, p < 0.001), transmission (incidence rate ratio 0.29, 95% CI: 0.13 to 0.65, p = 0.002), and surgical site infections (odds ratio 0.58, 95% CI: 0.40 to 0.86, p = 0.007). Increased duration of preoperative decolonization therapy was associated with decreased postoperative MRSA colonization (odds ratio 0.73, 95% CI: 0.53 to 1.00, p = 0.05). CONCLUSIONS: Preoperative S aureus screening with targeted decolonization was associated with reduced MRSA colonization, transmission, and surgical site infections. Duration of preoperative therapy correlated with decreased frequency of postoperative MRSA colonization.

Accumulation and cellular localization of nanoparticles in an ex vivo model of acute lung injury.

BACKGROUND: The benefit of nanomedicine in mitigating acute lung injury (ALI) is currently unknown. Therefore, we introduced the generation IV polyamidoamine dendrimers with neutral surface property (dendrimer) into our established ex vivo animal model and sought to determine their biodistribution to define their cellular uptake profile and to evaluate their potential as a drug delivery candidate for the treatment of ischemia-reperfusion-induced ALI. METHODS: Eight rabbit heart-lung blocks were harvested and exposed to 18 h of cold ischemia. The heart-lung blocks were then reperfused with rabbit donor blood. Dendrimer was conjugated to fluorescein isothiocyanate (D-FITC) for localization and quantification studies. D-FITC (30 mg or 150 mg) was injected into the bypass circuit and baseline, 1- and 2-h tissue samples were obtained to determine percent uptake. Low (10×) and high (40×) magnification images were obtained using confocal microscopy to confirm the accumulation and to determine the cellular targets of the dendrimer. RESULTS: Four heart-lung blocks were exposed to 30 mg and four to 150 mg of D-FITC. After adjusting for dry weight, the mean uptake in the 30 and 150 mg samples after 2 h of reperfusion were 0.79 ± 0.16% and 0.39 ± 0.22% of perfused doses, respectively. Confocal imaging demonstrated dendrimer uptake in epithelial cells and macrophages. CONCLUSIONS: Fluorescently tagged dendrimers demonstrated injury-dependent tissue accumulation in a variety of different cell types. This unique approach will allow conjugation to and delivery of multiple agents with the potential of mitigating ALI injury while avoiding systemic toxicity.

Development and Validation of a Score to Predict the Risk of Readmission After Adult Cardiac Operations.

BACKGROUND: The purpose of this study was to develop and validate a risk score for readmissions after cardiac operations. METHODS: Adults surviving to discharge after cardiac operations at a single institution from 2008 to 2013 were randomly divided 3:1 into training and validation cohorts. The primary outcome was readmission within 30 days of discharge. A multivariable model was constructed in the training cohort incorporating variables associated with 30-day readmission in univariate logistic regression. Points were assigned to predictors in the multivariable model proportional to their odds ratios. RESULTS: Among 5,193 patients undergoing cardiac operations and surviving to discharge, the 30-day readmission rate was 10.3% (n = 537). The most common reasons for readmission were volume overload (24%; n = 131) and infection (21%; n = 113). The risk score incorporated 5 multivariable predictors and was out of 20 possible points. The predicted rate of 30-day readmission based on the training cohort ranged from 5.9% (score = 0) to 54.7% (score = 20). Patients were categorized as low (score = 0; readmission 5.7%), moderate (score 1-7; readmission 11.0%), and high risk (score >7; readmission 24.2%) (p < 0.001). Thirty-day readmission rates based on these score categories were similar in the validation cohort (low 6.4%, moderate 11.0%, high 17.4%; p < 0.001). There was a robust correlation between predicted rates of readmission in the training cohort based on the composite risk score and actual rates of readmission in the validation cohort (r = 0.95; p < 0.001). CONCLUSIONS: We developed and validated a risk score for readmission after cardiac operations that may have utility in targeting interventions and modifying risk factors in high-risk populations.

Association Between Prolonged Graft Ischemia and Primary Graft Failure or Survival Following Lung Transplantation.

IMPORTANCE: The effect of prolonged graft ischemia (≥6 hours) on outcomes following lung transplantation is controversial. OBJECTIVE: To evaluate the effect of prolonged total graft ischemia times on long-term survival rates and the development of primary graft failure (PGF) following lung transplantation. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective study, the United Network for Organ Sharing database was queried for adult patients who underwent lung transplantation from May 1, 2005, through December 31, 2011. Primary stratification by the presence of prolonged graft ischemia was performed. Kaplan-Meier estimates at 1 and 5 years were used to compare survival in the 2 cohorts. A multivariable Cox proportional hazards regression model was constructed to identify predictors of 1- and 5-year mortality. A risk-adjusted predictive model for the development of PGF was formulated in a similar fashion. MAIN OUTCOMES AND MEASURES: The primary outcome of interest was 1- and 5-year survival. Secondary outcomes included PGF and other postoperative events, such as renal failure, biopsy-proven rejection, and stroke. RESULTS: Of the 10,225 patients who underwent lung transplantation, 3127 (30.6%) had allografts exposed to prolonged ischemia. There was no difference in survival at 1 (83.6% [95% CI, 82.3%-84.9%] vs 84.1% [95% CI, 83.3%-85.0%]; P = .41) or 5 (52.5% [95% CI, 51.0%-54.0%] vs 53.5% [95% CI, 51.3%-55.6%]; P = .82) years between patients who received grafts that were or were not exposed to ischemia that lasted 6 hours or more, respectively. Prolonged graft ischemia did not independently predict 1- or 5-year mortality or the development of PGF (odds ratio, 1.11; 95% CI, 0.88-1.39; P = .37). Furthermore, prolonged ischemia did not independently predict 1-year (hazard ratio, 1.09; 95% CI, 0.97-1.22; P =.15) or 5-year (hazard ratio, 1.05; 95% CI, 0.98-1.14; P =.18) mortality or the development of PGF (odds ratio, 1.11; 95% CI, 0.88-1.39; P =.37). CONCLUSIONS AND RELEVANCE: No association was found between prolonged total graft ischemia times and primary graft failure or survival following lung transplantation. Given the scarcity of organs and the paucity of suitable recipients, prolonged ischemia time should not preclude transplantation. It is, therefore, reasonable to consider extending the accepted period of ischemia to more than 6 hours in certain patient populations to improve organ use.

Clinicopathologic Presentation and Natural History of Anorectal Melanoma: A Case Series of 18 Patients.

Anorectal melanoma is a rare malignant neoplasm with variable natural history and nonspecific presentation. We describe the clinicopathologic and prognostic parameters of a series of 18 patients (16 [88.9%] white; 10 [55.6%] male; median age, 64.0 years [interquartile range, 45.8-74.3 years]) with histologically proven anorectal melanoma treated at our institution during a 21-year period between October 1991 and August 2012. Late diagnosis was common (44.5% of patients had stage II disease or worse at diagnosis), likely owing to a delay in presentation, nonspecific presenting symptoms, and frequent incorrect diagnoses (16 cases [88.9%]). Overall disease-specific mortality was 66.7% (12 of 18 patients), with a median time to death of 15.5 months (interquartile range, 7.3-25.5 months). Disease-specific survival was significantly better following wide local excision vs abdominoperineal resection (P = .04), although patients undergoing the former tended to have fewer rectal lesions (P = .04), smaller lesions (P = .02), and a trend toward less advanced stage (P = .06). Larger studies assessing optimal medical and surgical management for anorectal melanoma are needed to improve outcomes.